Inactivating tumor suppressor Ikaros mutations are associated in humans with high-risk B-cell leukemia resistant to treatment. The authors assessed Ikaros function on cell cycle regulation in various in vitro and in vivo assays (the latter on mouse xenograft models) and showed that decreased Ikaros activity due to the deletion or inactivating mutation of a single IKZF1 allele results in repression of genes regulation cell cycle promotion. Ikaros function was impaired by the pro-oncogenic casein kinase II (CK2), and CK2 is overexpressed in leukemia. CK2 inhibition restored Ikaros function as transcriptional repressor of cell cycle, resulting in an antileukemia effect. CK2 inhibition on mouse xenografts led to decrease in leukemic burden

* Restoration of Ikaros tumor suppressor activity via inhibition of CK2 might be a new target in high-risk leukemia with deletion of one IKZF1 allele.